Dr. Scheinman is a nephrologist beginning his faculty career as Assistant Professor of Medicine at S.U.N.Y.-Upstate Medical Center. He received his M.D. degree and residency training in Internal Medicine at Yale, and nephrology subspecialty training at both Upstate and Yale. During his research training he adapted the isolated perfused rat kidney for use as an in vitro model of parathyroid hormone effects. His goal is to establish himself as a major independent laboratory investigator, and he proposes initially to study a substantial unsolved problem in the regulation of inorganic phosphate (Pi) homeostasis: the nature of the signal that alters renal Pi reabsorption during changes in body Pi supply. The proposed studies will examine (1) whether Pi can directly influence renal Pi transport; (2) the relationship between extracellular or dietary pi and renal intracellular Pi; and (3) the existence of an extrarenal signal governing renal Pi reabsorption. A direct role of Pi will be examined using a new model for studying the regulation of renal transport: rat kidneys will be perfused in vitro with media of various compositions, and BBMV will be made from these kidneys and studied. Intracellular Pi will be assessed in perfused kidneys, and possibly kidneys in vivo, using the new technique of 31P-NMR spectroscopy. Finally, a model will be developed of renal adaptation to changes in Pi supply during parenteral nutrition in rats, and this model will be used to determine the importance of the gastrointestinal tract in this renal adaptation. Such studies may eventually shed light on a variety of conditions in which Pi homeostasis is disordered, possibly including vitamin D-resistant hypophosphatemic rickets, renal insufficiency, and certain forms of renal stone disease. Dr. Irwin M. Weiner will serve as sponsor, and Dr. George C. Levey as secondary sponsor will direct the NMR studies. Through Dr. Levy, Dr. Scheinman will have access to the N.I.H. Resource for Multinuclei NMR and Data Processing located at Syracuse University. Dr. Mary Ellen Trimble will collaborate on the BBMV studies, and Dr. Michael Meguid will collaborate on studies involving parental nutrition. In addition, the SUNY-Upstate Medical Center has many scientists active in renal physiology and a long tradition of interdisciplinary consultation.